Efficacy and safety of combining short-course neoadjuvant chemoradiotherapy with envafolimab in locally advanced rectal cancer patients with microsatellite stability: A phase II PRECAM experimental study.

BACKGROUND: Conventional neoadjuvant chemoradiotherapy (nCRT) yields a pathologic complete response (pCR) rate of 15%-30% for locally advanced rectal cancer (LARC). This study ventures to shift this paradigm by incorporating short-course nCRT with immunotherapy, specifically Envafolimab, to achieve improved treatment efficacy and possibly redefine the standard of care for LARC. MATERIALS AND METHODS: The PRECAM study is a prospective, single-arm, phase 2 clinical trial for LARC in patients with microsatellite stable (MSS) tumors. Participants received short-course radiotherapy (25Gy/5f), followed by two cycles of CAPEOX chemotherapy and six weekly doses of Envafolimab, a PD-L1 antibody, before total mesorectal excision surgery. The primary endpoint was the pCR rate. RESULTS: From April to December 2022, 34 patients were enrolled, of whom 32 completed the study, each diagnosed with an MSS rectal adenocarcinoma. All patients underwent preoperative CRT combined with Envafolimab. Remarkably, a pCR rate of 62.5% (20/32) was attained, and a significant pathologic response rate of 75% (24/32) was achieved. Additionally, 21 of 32 participants achieved a neoadjuvant rectal (NAR) score below 8, suggesting an effective treatment response. Common adverse events included tenesmus (78.1%), diarrhea (62.5%), and leukocyte decrease (40.6%). Two Grade 3 adverse events were noted, one related to liver function abnormality and the other to a decrease in platelet count. Surgical procedures were performed in all cases, with minor complications, including ileus, infections, and anastomotic leakage. As of this report, there have been no reported cases of recurrence or death during the follow-up period, ranging from 12 to 20 months. CONCLUSION: In LARC patients exhibiting MSS tumors, combining short-course nCRT with Envafolimab demonstrated favorable efficacy, leading to a significant pCR rate. Minor adverse effects and surgical complications were observed. These preliminary but promising results underscore the potential of this approach and call for further exploration and validation through a randomized controlled trial.

18F-FDG PET/CT imaging and curative effect evaluation of multiple muscular tuberculosis.

Tuberculosis continues to be a significant global health concern, impacting various parts of the body aside from the lungs. Muscular tuberculosis (MT), while rare, poses diagnostic hurdles due to its nonspecific imaging features. Presenting a case of a 66-year-old man with multiple MT lesions, we underscore the vital contribution of positron emission tomography/computed tomography (PET/CT) in both diagnosis and treatment assessment. Fluorine-18-fluorodeoxyglucose (18F-FDG) PET/CT imaging revealed hypermetabolism in bilateral chest and back muscles, facilitating accurate diagnosis and monitoring treatment response. This highlights the pivotal role of 18F-FDG PET/CT in managing MT, especially in cases with multiple lesions.

Transient Covalency in Molten Uranium(III) Chloride.

Uranium is arguably the most essential element in the actinide series, serving as a crucial component of nuclear fuels. While U is recognized for engaging the 5f orbitals in chemical bonds under normal conditions, little is known about its coordination chemistry and the nature of bonding interactions at extreme conditions of high temperature. Here we report experimental and computational evidence for the shrinkage of the average U-ligand distance in UCl3 upon the solid-to-molten phase transition, leading to the formation of a significant fraction of short, transient U-Cl bonds with the enhanced involvement of U 5f valence orbitals. These findings reveal that extreme temperatures create an unusual heterogeneous bonding environment around U(III) with distinct inner- and outer-coordination subshells.

Deubiquitination of aryl hydrocarbon receptor (AhR) by USP21 negatively regulates Th17 cells differentiation.

Aryl hydrocarbon receptor (AhR) is a key transcription factor that modulates the differentiation of T helper 17 (Th17) cells. How AhR is regulated at the post-translational level in Th17 cells remains largely unclear. Here we identify USP21 as a newly defined deubiquitinase of AhR. We demonstrate that USP21 interacts with and stabilizes AhR by removing the K48-linked polyubiquitin chains from AhR. Interestingly, USP21 inhibits the transcriptional activity of AhR in a deubiquitinating-dependent manner. USP21 deubiquitinates AhR at the K432 residue, and the maintenance of ubiquitination on this site is required for the intact transcriptional activity of AhR. Moreover, the deficiency of USP21 promotes the differentiation of Th17 cells both in vitro and in vivo. Consistently, adoptive transfer of USP21 deficient naïve CD4+ T cells elicits more severe colitis in Rag1-/- recipients. Therefore, our study reveals a novel mechanism in which USP21 deubiquitinates AhR and negatively regulates the differentiation of Th17 cells.

Forkhead box M1 mediates metabolic reprogramming in human colorectal cancer cells.

Metabolic reprogramming is recognized as a hallmark of cancer, enabling cancer cells to acquire essential biomolecules for cell growth, often characterized by upregulated glycolysis and/or fatty acid synthesis-related genes. The transcription factor forkhead box M1 (FOXM1) has been implicated in various cancers, contributing significantly to their development, including colorectal cancer (CRC), a major global health concern. Despite FOXM1's established role in cancer, its specific involvement in the Warburg effect and fatty acid biosynthesis in CRC remains unclear. We analyzed The Cancer Genome Atlas (TCGA) Colonic Adenocarcinoma and Rectal Adenocarcinoma (COADREAD) datasets to to derive the correlation of the expression levels between FOXM1 and multiple genes and the survival prognosis based on FOXM1 expression. Using two human CRC cell lines, HT29 and HCT116, we conducted RNAi or plasmid transfection procedures, followed by a series of assays, including RNA extraction, quantitative real-time polymerase chain reaction, Western blot analysis, cell metabolic assays, and immunofluorescence analysis. Higher expression levels of FOXM1 correlated with a poorer survival prognosis, and the expression of FOXM1 was positively correlated with glycolysis-related genes SLC2A1 and LDHA, de novo lipogenesis-related genes ACACA and FASN, and MYC. FOXM1 appeared to modulate AKT/mTOR signaling, the expression of c-Myc, proteins related to glycolysis and fatty acid biosynthesis, as well as extracellular acidification rate in HT29 and HCT116 cells. In summary, FOXM1 plays a regulatory role in glycolysis, fatty acid biosynthesis, and cellular energy consumption, thereby influencing CRC cell growth and patient prognosis.

High-Density Dual-Structure Single-Atom Pt Electrocatalyst for Efficient Hydrogen Evolution and Multimodal Sensing.

Herein, we report a high-density dual-structure single-atom catalyst (SAC) by creating a large number of vacancies of O and Ti in two-dimensional (2D) Ti3C2 to immobilize Pt atoms (SA Pt-Ti3C2). The SA Pt-Ti3C2 showed excellent performance toward the pH-universal electrochemical hydrogen evolution reaction (HER) and multimodal sensing. For HER catalysis, compared to the commercial 20 wt % Pt/C, the Pt mass activities of SA Pt-Ti3C2 at the overpotentials of ∼30 and 110 mV in acid and alkaline media are 45 and 34 times higher, respectively. More importantly, during the alkaline HER process, an interesting synergetic effect between Pt-C and Pt-Ti sites that dominated the Volmer and Heyrovsky steps, respectively, was revealed. Moreover, the SA Pt-Ti3C2 catalyst exhibited high sensitivity (0.62-2.65 µA µM-1) and fast response properties for the multimodal identifications of ascorbic acid, dopamine, uric acid, and nitric oxide under the assistance of machine learning.

Influence of Heat Treatment Condition on the Microstructure, Microhardness and Corrosion Resistance of Ag-Sn-In-Ni-Te Alloy Wire.

Ag-Sn-In-Ni-Te alloy ingots were produced through a heating-cooling combined mold continuous casting technique; they were then drawn into wires. However, during the drawing process, the alloy wires tended to harden, making further diameter reduction challenging. To overcome this, heat treatment was necessary to soften the previously drawn wires. The study investigated how variations in heat treatment temperature and holding time affected the microstructure, microhardness and corrosion resistance of the alloy wires. The results indicate that the alloy wires subjected to heat treatment at 700 °C for 2 h not only exhibited a uniform microstructure distribution, but also demonstrated low microhardness and excellent corrosion resistance.

Exploring Cr and molten salt interfacial interactions for molten salt applications.

Molten salts play an important role in various energy-related applications such as high-temperature heat transfer fluids and reaction media. However, the extreme molten salt environment causes the degradation of materials, raising safety and sustainability challenges. A fundamental understanding of material-molten salt interfacial evolution is needed. This work studies the transformation of metallic Cr in molten 50/50 mol% KCl-MgCl2via multi-modal in situ synchrotron X-ray nano-tomography, diffraction and spectroscopy combined with density functional theory (DFT) and ab initio molecular dynamics (AIMD) simulations. Notably, in addition to the dissolution of Cr in the molten salt to form porous structures, a δ-A15 Cr phase was found to gradually form as a result of the metal-salt interaction. This phase change of Cr is associated with a change in the coordination environment of Cr at the interface. DFT and AIMD simulations provide a basis for understanding the enhanced stability of δ-A15 Cr vs. bcc Cr, by revealing their competitive phase thermodynamics at elevated temperatures and probing the interfacial behavior of the molten salt at relevant facets. This study provides critical insights into the morphological and chemical evolution of metal-molten salt interfaces. The combination of multimodal synchrotron analysis and atomic simulation also offers an opportunity to explore a broader range of systems critical to energy applications.

In situ fabrication of atomically adjacent dual-vacancy sites for nearly 100% selective CH4 production.

The photocatalytic CO2-to-CH4 conversion involves multiple consecutive proton-electron coupling transfer processes. Achieving high CH4 selectivity with satisfactory conversion efficiency remains challenging since the inefficient proton and electron delivery path results in sluggish proton-electron transfer kinetics. Herein, we propose the fabrication of atomically adjacent anion-cation vacancy as paired redox active sites that could maximally promote the proton- and electron-donating efficiency to simultaneously enhance the oxidation and reduction half-reactions, achieving higher photocatalytic CO2 reduction activity and CH4 selectivity. Taking TiO2 as a photocatalyst prototype, the operando electron paramagnetic resonance spectra, quasi in situ X-ray photoelectron spectroscopy measurements, and high-angle annular dark-field-scanning transmission electron microscopy image analysis prove that the VTi on TiO2 as initial sites can induce electron redistribution and facilitate the escape of the adjacent oxygen atom, thereby triggering the dynamic creation of atomically adjacent dual-vacancy sites during photocatalytic reactions. The dual-vacancy sites not only promote the proton- and electron-donating efficiency for CO2 activation and protonation but also modulate the coordination modes of surface-bound intermediate species, thus converting the endoergic protonation step to an exoergic reaction process and steering the CO2 reduction pathway toward CH4 production. As a result, these in situ created dual active sites enable nearly 100% CH4 selectivity and evolution rate of 19.4 µmol g-1 h-1, about 80 times higher than that of pristine TiO2. Thus, these insights into vacancy dynamics and structure-function relationship are valuable to atomic understanding and catalyst design for achieving highly selective catalysis.

Iridium Single Atoms to Nanoparticles: Nurturing the Local Synergy with Cobalt-Oxide Supported Palladium Nanoparticles for Oxygen Reduction Reaction.

A ternary catalyst comprising Iridium (Ir) single-atoms (SA)s decorated on the Co-oxide supported palladium (Pd) nanoparticles (denoted as CPI-SA) is developed in this work. The CPI-SA with 1 wt.% of Ir exhibits unprecedented high mass activity (MA) of 7173 and 770 mA mgIr -1, respectively, at 0.85 and 0.90 V versus RHE in alkaline ORR (0.1 m KOH), outperforming the commercial Johnson Matthey Pt catalyst (J.M.-Pt/C; 20 wt.% Pt) by 107-folds. More importantly, the high structural reliability of the Ir single-atoms endows the CPI-SA with outstanding durability, where it shows progressively increasing MA of 13 342 and 1372 mA mgIr -1, respectively, at 0.85 and 0.90 V versus RHE up to 69 000 cycles (3 months) in the accelerated degradation test (ADT). Evidence from the in situ partial fluorescence yield X-ray absorption spectroscopy (PFY-XAS) and the electrochemical analysis indicate that the Ir single-atoms and adjacent Pd domains synergistically promote the O2 splitting and subsequent desorption of hydroxide ions (OH-), respectively. Whereas the Co-atoms underneath serve as electron injectors to boost the ORR activity of the Ir single-atoms. Besides, a progressive and sharp drop in the ORR performance is observed when Ir-clusters and Ir nanoparticles are decorated on the Co-oxide-supported Pd nanoparticles.

Enhanced Catalytic Oxidation Reactivity over Atomically Dispersed Pt/CeO2 Catalysts by CO Activation.

The elevation of the low-temperature oxidation activity for Pt/CeO2 catalysts is challenging to meet the increasingly stringent requirements for effectively eliminating carbon monoxide (CO) from automobile exhaust. Although reducing activation is a facile strategy for boosting reactivity, past research has mainly concentrated on applying H2 as the reductant, ignoring the reduction capabilities of CO itself, a prevalent component of automobile exhaust. Herein, atomically dispersed Pt/CeO2 was fabricated and activated by CO, which could lower the 90% conversion temperature (T90) by 256 °C and achieve a 20-fold higher CO consumption rate at 200 °C. The activated Pt/CeO2 catalysts showed exceptional catalytic oxidation activity and robust hydrothermal stability under the simulated working conditions for gasoline or diesel exhausts. Characterization results illustrated that the CO activation triggered the formation of a large portion of Pt0 terrace sites, acting as inherent active sites for CO oxidation. Besides, CO activation weakened the Pt-O-Ce bond strength to generate a surface oxygen vacancy (Vo). It served as the oxygen reservoir to store the dissociated oxygen and convert it into active dioxygen intermediates. Conversely, H2 activation failed to stimulate Vo, but triggered a deactivating transformation of the Pt nanocluster into inactive PtxOy in the presence of oxygen. The present work offers coherent insight into the upsurging effect of CO activation on Pt/CeO2, aiming to set up a valuable avenue in elevating the efficiency of eliminating CO, C3H6, and NH3 from automobile exhaust.

Highly Stable and Selective Ni/ZrO2 Nanofiber Catalysts for Efficient CO2 Methanation.

Ni-based oxides are promising catalysts for CO2 methanation. However, Ni-based catalysts also have some unresolved issues and drawbacks in practical applications. The activity and selectivity of Ni-based catalysts in CO2 methanation at low temperatures still need to be improved. Here, Ni/ZrO2 nanofibers with high surface areas (up to 101.2 m2/g) were prepared by electrospinning methods. The Ni/ZrO2-ES (also named as 66Ni/ZrO2) catalyst showed excellent catalytic performance in CO2 methanation (the CO2 conversion = 81% and CH4 selectivity = 99% at 350 °C) and excellent stability for 100 h, which was better than most reported Ni/ZrO2 catalysts. However, the comparison sample Ni/ZrO2-CP prepared by the coprecipitation method had poor catalytic performance (the CO2 conversion = 54% and CH4 selectivity = 90% at 350 °C). Within 100 h, the CO2 conversion decreased to 30% and the CH4 selectivity decreased to 52%. Both EPR and O1S XPS confirmed that Ni/ZrO2 nanofibers can form more reactive oxygen species vacancies, and CO2-TPD confirmed that nanofibers had more CO2 adsorption sites compared with the control sample Ni/ZrO2-CP. In situ DRIFTS analysis showed that bidentate carbonate and monodentate carbonate were key intermediates in CO2 methanation. The catalytic performance of Ni/ZrO2 nanofiber catalysts would be attributed to higher dispersion of Ni species on the surface of nanofibers, high specific surface area (101.2 m2/g), more oxygen vacancies, more CO2 adsorption sites, and the synergistic effect between Ni nanoparticles and ZrO2 nanofibers. This work may inspire the rational design of Ni/ZrO2 nanofiber catalysts with rich oxygen vacancies for low-temperature CO2 methanation.

Preparation, Structures, Photoluminescence and Semiconductive Properties of Two Novel Lanthanide Mercury Materials with a 3-D Framework Structure.

Two novel lanthanide mercury materials, [Gd(IA)3(H3O)2Hg3Br6]n·2nCl (1) and [La(IA)3(H3O)2Hg3Br6]n·2nCl (2) (IA = isonicotinic anion), have been prepared under solvothermal conditions and characterized by single-crystal X-ray diffraction techniques. They are isomorphic and characterized by a three-dimensional (3-D) framework structure. The lanthanide ions are bound by eight oxygen atoms to exhibit a square antiprismatic geometry. The solid-state photoluminescence experiment discovers that compound 1 shows a strong emission in the red region. Compound 1 possesses CIE (Commission Internationale de I'Éclairage) chromaticity coordinates of 0.7347 and 0.2653. Its CCT (correlated color temperature) is 6514 K. Compound 2 displays yellow photoluminescence and it has CIE chromaticity coordinates of 0.4411 and 0.5151. The CCT of compound 2 is 3633 K. Solid-state UV/Vis diffuse reflectance spectra revealed that their semiconductor band gaps are 2.16 eV and 2.85 eV, respectively.

Supramolecular Complexation-enhanced CO2 Chemisorption in Amine-derived Sorbents.

A supramolecular complexation approach is developed to improve the CO2 chemisorption performance of solvent-lean amine sorbents. Operando spectroscopy techniques reveal the formation of carbamic acid in the presence of a crown ether. The reaction pathway is confirmed by theoretical simulation, in which the crown ether acts as proton acceptor and shuttle to drive the formation and stabilization of carbamic acid. Improved CO2 capacity and diminished energy consumption in sorbent regeneration was achieved.

Multiple Functional Bonds Integrated Interphases for Long Cycle Sodium-Ion Batteries.

Sodium-ion batteries (SIBs) have garnered significant interest as one of the most promising energy suppliers for power grid energy storage. However, the poor electrode/electrolyte interfacial stability leads to continual electrolyte decomposition and transition metal dissolution, resulting in rapid performance degradation of SIBs. In this work, we propose a strategy integrating multiple functional bonds to regulate electrode/electrolyte interphase by triple-coupling of succinonitrile (SN), sodium hexafluorophosphate (NaPF6) and fluorinated ethylene carbonate (FEC). Theoretical calculation and experiment results show that the solvation structure of Na+ and ClO4- is effectively reconfigured by the solvated FEC, SN and PF6- in PC-based carbonate electrolyte. The newly developed electrolyte demonstrates increased Na+-FEC coordination, weakened interaction of Na+-PC and participation of SN and PF6- anions in solvation, resulting in the formation of a conformal interfacial layer comprising of sodium oxynitrides (NaNxOy), sodium fluoride (NaF) and phosphorus oxide compounds (NaPxOy). Consequently, a 3 Ah pouch full cell of hard carbon//NaNi1/3Fe1/3Mn1/3O2 exhibits an excellent capacity retention of 90.4% after 1000 cycles. Detailed postmortem analysis of interface chemistry is further illustrated by multiple characterization methods. This study provides a new avenue for developing electrolyte formulations with multiple functional bonds integrated interphases to significantly improve the long-term cycling stability of SIBs.

Elemental analysis of levitated solid samples by microwave-assisted laser induced breakdown spectroscopy.

A novel analysis technique of elements at ambient conditions has been developed. The technique is based on microwave-assisted laser-induced breakdown spectroscopy (MW-LIBS) applied to acoustically levitated samples. The technique has been demonstrated using three solid samples with different properties and compositions. These are ore containing multiple elements (OREAS 520), aluminium oxide (Al3O2) and gypsum (CaSO4·2H2O). The mass of samples was 21 mg, 23 mg, and 55 mg for gypsum, mineral ore, and Al3O2, respectively. Significant signal enhancements were recorded for a variety of elements, using microwave-assisted laser-induced breakdown spectroscopy and levitation (MW-LIBS-Levitation). The signal enhancement for Mn I (403.07 nm), Al I (396.13 nm) and Ca II (393.85 nm) was determined as 123, 46, and 63 times, respectively. Moreover, it was found that MW-LIBS-Levitation minimises the self-absorption of the Ca I (422.67 nm) and Na I (588.99 nm and 589.59 nm) spectral lines. In addition to the signal enhancements, the levitation process produces a spinning motion in the solids with an angular frequency of 7 Hz. This feature benefits laser-based analysis as a fresh sample is introduced at each laser pulse, eliminating the need for the usual mechanical devices. Based on the single-shot analysis, it was found that ∼80% of the laser pulses produced successful MW-LIBS-Levitation detection, confirming an impressive repeatability of the process. This contactless analytical technique can be applied in ambient pressure and temperature conditions with high sensitivity, which can benefit disciplines such as forensics science, isotope analysis, and medical analysis, where the sample availability is often diminutive.

Classics in abdominal imaging: the "Lollipop sign" of epithelioid hemangioendothelioma.

A 58-year-old female was diagnosed with epithelioid hemangioendothelioma (EHE). The intrahepatic lesion exhibited a "Lollipop sign," associated with capsular retraction. On the PET/CT, there are multiple lesions in the lungs with variable high and low FDG uptake, and focal calcifications are present on CT. Additionally, destruction of the thoracic vertebrae has been observed.

Enabling direct oxidation of ethane to acetaldehyde with oxygen using supported PdO nanoparticles.

Industrial-scale production of acetaldehyde relies heavily on homogeneous catalysts. Here, we used ethane as the feedstock and developed ZSM-5-supported PdO nanoparticles for the direct oxidation of ethane to acetaldehyde by utilizing O2 and CO. PdO nanoparticles clearly demonstrate effective activity and prevent the further deep oxidation of acetaldehyde.

Cannabinoid receptor 2 selective agonist alleviates systemic sclerosis by inhibiting Th2 differentiation through JAK/SOCS3 signaling.

Systemic sclerosis (SSc) poses a significant challenge in autoimmunology, characterized by the development of debilitating fibrosis of skin and internal organs. The pivotal role of dysregulated T cells, notably the skewed polarization toward Th2 cells, has been implicated in the vascular damage and progressive fibrosis observed in SSc. In this study, we explored the underlying mechanisms by which cannabinoid receptor 2 (CB2) highly selective agonist HU-308 restores the imbalance of T cells to alleviate SSc. Using a bleomycin-induced SSc (BLM-SSc) mouse model, we demonstrated that HU-308 effectively attenuates skin and lung fibrosis by specifically activating CB2 on CD4+ T cells to inhibit the polarization of Th2 cells in BLM-SSc mice, which was validated by Cnr2-specific-deficient mice. Different from classical signaling downstream of G protein-coupled receptors (GPCRs), HU-308 facilitates the expression of SOCS3 protein and subsequently impedes the IL2/STAT5 signaling pathway during Th2 differentiation. The deficiency of SOCS3 partially mitigated the impact of HU-308. Analysis of a cohort comprising 80 SSc patients and 82 healthy controls revealed an abnormal elevation in the Th2/Th1 ratio in SSc patients. The proportion of Th2 cells showed a significant positive correlation with mRSS score and positivity of anti-Scl-70. Administration of HU-308 to PBMCs and peripheral CD4+ T cells from SSc patients led to the upregulation of SOCS3, which effectively suppressed the aberrantly activated STAT5 signaling pathway and the proportion of CD4+IL4+ T cells. In conclusion, our findings unveil a novel mechanism by which the CB2 agonist HU-308 ameliorates fibrosis in SSc by targeting and reducing Th2 responses. These insights provide a foundation for future therapeutic approaches in SSc by modulating Th2 responses.

Solidophobic Surface for Electrochemical Extraction of High-Valued Mg(OH)2 Coupled with H2 Production from Seawater.

A significant challenge in direct seawater electrolysis is the rapid deactivation of the cathode due to the large scaling of Mg(OH)2. Herein, we synthesized a Pt-coated highly disordered NiCu alloy (Pt-NiCu alloy) electrode with superior solidophobic behavior, enabling stable hydrogen generation (100 mA cm-2, >1000 h durability) and simultaneous production of Mg(OH)2 (>99.0% purity) in electrolyte enriched with Mg2+ and Ca2+. The unconventional solidophobic property primarily stems from the high surface energy of the NiCu alloy substrate, which facilitates the adsorption of surface water and thereby compels the bulk formation of Mg(OH)2 via homogeneous nucleation. The discovery of this solidophobic electrode will revolutionarily simplify the existing techniques for seawater electrolysis and increase the economic viability for seawater electrolysis.